Lubricious coating

ABSTRACT

A lubricant coating vehicle for medical devices used to reduce the coefficient of friction of such devices upon exposure thereof to moisture. The lubricant coating vehicle allows the introduction of a pharmacological additive having a release rate that is within acceptable pharmacokinetic criteria. The release rate is adjusted by utilizing different salt forms of the additive and adjusting the concentration of a urethane pre-polymer.

CROSS-REFERENCE TO RELATED APPLICATIONS

This Patent Application is a Continuation of U.S. patent applicationSer. No. 10/691,853, filed Oct. 23, 2003, the contents of which areincorporated herein by reference in their entirety.

BACKGROUND

1. Technical Field

The present invention relates to a lubricant coating for medicaldevices, and more particularly, to a hydrophilic polymeric coating whichaids medical devices to become slippery when wetted. The lubricantcoating of the present invention may be employed to reduce thecoefficient of friction of catheters, arterial venous shunts,gastroenteric feed tubes, endotracheal tubes and other medical implantsor polymeric substrates. The coating of the present invention alsoincorporates additive compounds such as anti-microbial that are releasedin a pharmaceutically acceptable manner. Methods are also provided forthe manufacture of the subject lubricant coating and for the applicationof the same to surfaces of medical devices.

2. Background of the Related Art

Known lubricant coatings applied to surfaces of medical devices includecoatings of polyvinylpyrrolidone, polyurethane, acrylic polyester, vinylresin, fluorocarbons, silicone rubber, and combinations of thesesubstances. For example, Micklus et al., U.S. Pat. Nos. 4,100,309 and4,119,094, relate to a hydrophilic coating ofpolyvinylpyrrolidone-polyurethane interpolymer formed usingpolyisocyanate. Ratner et al., U.S. Pat. No. 3,939,049, relates to amethod of grafting hydrogels for lubrication to polymeric substratesusing radiation. Hungton et al. U.S. Pat. No. 3,975,350, relates tohydrophilic polyurethane polymers for use as lubricants. Storey. et al.U.S. Pat. No. 3,987,497, relates to a tendon prosthesis having alubricant hydrogel coating. Many known lubricious coatings are prone tovarious disadvantages when used in the medical field. Disadvantages ofsuch known lubricants may include insufficiently low coefficient offriction, lack of permanence such as characteristic of silicone orfluorocarbon based coatings, slipperiness when dry as well as wet thusmaking handling difficult, utilization of hazardous solvents in themanufacture of the same and utilization of unstable reactive materialsin the manufacture of the same. Lubricants produced for medical use fromunstable reactive material often require the coating solution to beprepared daily or more frequently to be useful and thereby increaseswaste and expense. Lubricants produced for medical use involvinghazardous solvents are undesirable due to patient toxicity concerns andOSHA considerations. Also, lubricant coatings provided for inducingforeign devices into various areas of the body that are susceptible toinfection and or hrombogenicreactions have failed to provide apharmaceutically acceptable carrier for anticrobial andanti-thrombogenic compounds.

In order to solve these and other potential disadvantages of knownlubricants such as those of the above-cited patents, which are hereby,incorporated herein by reference, a lubricant coating is needed thatwhen wetted has sufficient lubricity to be useful in the medical devicefield such as for medical implants and the ability to incorporate withinthat coating anti-microbial compounds that can be released in apharmaceutically acceptable manner. The lubricant coating must becapable of adhering to a wide variety of substrates and resist wetabrasion. It would also be desirable to have such a lubricant coatingprepared from chemically stable and biocompatible solvents. Further, itwould be advantageous to prepare such coating from components that arenot health hazards.

SUMMARY OF THE INVENTION

The present invention provides a lubricant coating compositioncomprising a hydrophilic polymer such as polyvinylpyrrolidone, apolyoxyethylene-based isocyanate-terminated prepolymer, an alkyl esterof a carboxylic acid and an alkylbenzene. The present invention alsoprovides a method of making the subject lubricant coating which adheresto a wide variety of substrates and resists wet abrasion. The subjectlubricant coating is chemically stable and is biocompatible as describedin greater detail below.

In an illustrative embodiment, the lubricant coating compositioncomprises a hydrophilic polymer, an isocyanate-terminated prepolymer, analkylester of a carboxylic acid, a solvent such as tetrahydrofliran(THF), a pharmaceutical additive and urethane. The urethane increasesthe binding strength of the inventive coating and controls the rate ofrelease of the pharmaceutical additive. The addition of the urethaneenables the pharmacokinetics of the anti-microbial or otherpharmacological additives to be within acceptable pharmaceutical limits.

In a further alternative illustrative embodiment, the lubricant coatingcomposition comprises a hydrophilic polymer such aspolyvinylpyrrolidone, a hexamethylene (HDI) isocyanate-terminatedprepolymer, an alkylester of a carboxylic acid and a solvent suchastetrahydrofuran (THF). It is contemplated within the scope of thisinvention that other solvents, in which HDI is soluble in, as is knownin the art can be used. These solvents include, but are not limited to,Dimethylformamide (DMF), Methylene chloride, Cyclohexanone or the like.

In an alternative illustrative embodiment, the lubricant coatingcomposition comprises a hydrophilic polymer such aspolyvinylpyrrolidone, a polyoxyethylene-based isocyanate-terminatedprepolymer, an alkylester of a carboxylic acid and a solvent such astetrahydrofuran (THF). The TKF in place of the alkylbenzene that is usedin an alternative illustrative embodiment imparts greater solubility ofcertain isocyanate-terminated prepolymers. It is contemplated within thescope of the invention that other solvents known in the art can be used,for example, Dimethylformamide (DMF), Methylene chloride, Cyclohexanoneor the like. It is contemplated within the scope of this invention thatthese solvents may be used alone or in combination with each other.

A method for using the subject lubricant coating composition to coatmedical devices is provided herein, which involves cleaning or washing,drying, dip coating or applying of the lubricant, air drying or removalof excess lubricant, and optionally baking and packaging a medicaldevice either before or after sterilization thereof.

The present invention also provides a medical device whereby at least aportion thereof is coated with the subject lubricant coating, which ischaracterized as being able to achieve a wetted lubricity with areduction of friction of more than fifty (50) percent.

The present invention also provides a vehicle for incorporating ananti-microbial or antithrombogenic agent having pharmaceuticallyacceptable pharmacokinetic properties without interfering with thelubricous nature of the coating.

DETAILED DESCRIPTION OF THE INVENTION

The lubricant coating of the present invention has been foundparticularly useful in lowering the coefficient of friction of medicaldevices such as indwelling thoracic catheters and other medical devices.The subject coating is manufactured from a blend of one or more C1-12alkylbenzenes such as, for example, toluene, xylene, or styrene, butpreferably toluene to increase stability, a C1-12 alkylester of acarboxylic acid such as, for example, ethyl lactate, methylbenzoate, orpropolyacrylate wherein ethyl lactate is preferred to increasestability, a polymer such as for example polyvinylpyrrolidone, polyvinylalcohol, polyacrylic acid or polyethylene oxide, but preferablypolyvinylpyrrolidone to increase hydrophilicity and lubricity, and anisocyanate-terminated prepolymer.

According to the invention, in some coatings it has been found thattetrahydrofuran (THF) in place of the alkylbenzene imparts greatersolubility of certain isocyanate-terminated prepolymers. It has alsobeen found advantageous to use other solvents known in the art thatinclude, but are not limited to, Dimethylformamide (DMF), methylenechloride, Cyclohexanone or the like.

Isocyanate-terminated prepolymer that can be used according to theinvention include, polyoxyethylene-based isocyanate such as a toluene orisophorone diisocyanate-based prepolymer such as, for example, Hypol*PreMA G60, manufactured by Hampshire Corporation of Lexington,Massachusetts, or Vibrathane @, a 4,4-diphenylmethane-disocyanante (MDI)urethane prepolymer, manufactured by Uniroyal, or Adiprene @, a low-freeTDI, manufactured by Uniroyal Chemical.

It is contemplated within the scope of the invention that otherisocyanate-terminated prepolymers known in the art may be used. Thesepreploymers include, but are not limited to, polytetramethylene etherglycol-diphenylmethane diisocyanate (MDI), polytetramethylene etherglycol-tolylene diisocyanate (TDI), polytetramethylene etherglycol-isophorone diisocyanate, poly(1,4-oxybutylene)glycol-diphenylmethane diisocyanate (MDI), poly(1,4-oxybutylene)glycol-tolylene diisocyanate (TDI), poly(1,4-oxybutylene)glycol-isophorone diisocyanate, polyethylene glycol-diphenylmethanediisocyanate (MDI), polyethylene glycol-tolylene diisocyanate (TDI),poly-ethylene glycol-isophorone diisocyanate, polypropyl-eneglycol-diphenylmethane diisocyanate (MDI), poly-propyleneglycol-tolylene diisocyanate (TDI), polypropylene glycol-isophoronediisocyanate, polycaprolac-tone-diphenylmethane diisocyanate (MDI),polycaprolactone-tolylene diisocyanate (TDI),polycaprolactone-isophorone diisocyanate, polyethyleneadipate-diphenylmethane diisocyanate (MDI), polyethyleneadipate-tolylene diisocyanate (TDI), polyethylene adipate-isophoronediisocyanate, polytetra-methylene adipate-diphenylmethane diisocyanate(MDI), polytetramethylene adipate-tolylene diisocyanate (TDI),polytetramethylen adipate-isophorone diisocyanate,polyethylene-propylene adipate-diphenylmethane diisocyanate (MDI),polyethylene-propylene adipate-tolylene, diisocyanate (TDI), orpolyethylene-propylene adipate-isophorone diisocyanate polyurethanes.

In an alternative illustrative embodiment, a hexamethylene (HDI)isocyanate-terminated prepolymer can be used. The HDIicocyanate-terminated prepolymers offer improvements in worker safety. AHDI that has been found useful in the coatings according to theinvention include, but is not limited to, Adiprene @ LFH 710, CromptonCorporation, Middlebury, Conn. This HDI provides anisocyanate-terminated prepolymer having less than about 0.1% free HDI,which can be beneficial in the management and control of worker exposureto HDI. This relatively low free HDI reduces dermal toxicity that can beassociated with other prior art isocyanate-terminated prepolymers.

It is contemplated within the scope of the invention that urethanes suchas Pellethane@, an aromatic ether polyurethane manufactured by DowChemical, or Hyrothane@, manufactured by CardioTech International, canbe used in addition to or currently with isocyanate-terminatedprepolymers to enhance binding strength. It is contemplated within thescope of the invention that other urethanes known in the art may beused.

The urethane increases the binding strength of the coating and controlsthe rate of release and thus enables the pharmacokinetics of theanti-microbial or other pharmacological additives to be withinacceptable pharmaceutical limits, and it covalently bindsanti-thrombogenic additives to prevent systematic absorption. Whiledifferent urethanes have different properties and may require differentsolvent systems, the durometer of the urethane must match the durometerof the medical device to be coated or the functionality of the medicaldevice may become compromised.

Solvent selection and blend ratio are important to provide adequatesolubility and inertness to the hydrophilic urethane and additives.Anti-microbial additives, such as silver salts or antibiotics, may beuniformly suspended within the coating solution. These additives arereleased on contact with moisture, the rate of release and thelubricious properties of the coating are controlled by altering theratio of urethane and PVP. For further examples of suitablepolyisocyanates see Encyclopedia of Polymer Science and Technology, H.F. Mark, N. G. Gaylord and N. M. Bikeles (eds.) (1969) incorporatedherein by reference.

Anti-microbial additives utilized within the present invention includethe biguanides, especially chlorhexidine and its salts, includingchlorhexidine acetate, chlorhexidine gluconate, chlorhexidinehydrochloride, and chlorhexidine sulfate, silver and its salts,including silver acetate, silver benzoate, silver carbonate, silveriodate, silver iodide, silver lactate, silver laurate, silver nitrate,silver oxide, silver palmitate, silver protein, and silver sulfadiazine,polymyxin, tetracycline, aminoglycosides, such as tobramycin andgentamicin, rifampician, bacitracin, neomycin, chloramphenical,miconazole, tolnaftate, quinolones such as oxolinic acid, norfloxacin,nalidix acid, pefloxacin, enoxacin and ciprofloxacin, penicillins suchas ampicillin, amoxicillin and piracil, cephalosporins, vancomycin, andcombinations of any of the above anti-microbials.

An anti-thrombogenic additive useful according to the present inventionwould be heparin. It is contemplated within the scope of the inventionthat modified forms of heparin may be used to ensure its biologicalactivity and anti-thrombogenic properties. It is further contemplatedthat the urethane component may be modified to more readily accept theheparin or modified heparin molecule. According to the invention,anti-thrombogenic additives such as heparin are blended into theurethane component of the coating mixture. Without being bound to anyparticular theory, it is believed that the heparin molecule is entrappedwithin the urethane substrate.

Additionally, organic compounds derived from plants and herbs havingdesirable pharmacological properties can be utilized. Extracts of plantsand herbs have been known to possess anti-microbial activity and theiruse has been shown to be safe for human and animal consumption. Extractsof such plants, known as phytochemicals, may be utilized for theirantimicrobial properties. Some of these extracts, such as grapefruitseed extract, Tea Tree Oil and Myrtle Oil and others can be incorporatedinto the lubricious coating vehicle and their antimicrobial propertiesreleased to the surrounding tissue in an efficacious manner.

In some illustrative embodiments of the present invention colorants,emulsifiers, surfactants, and color stabilizers that are well knownwithin the art are added to the coating formulation. The colorants inthe form of dyes or pigments aid in reducing shelf life discoloration ordiscoloration due to the effects of sterilization. The addition ofemulsifiers and surfactants aid in suspension stability of the lubricouscoating vehicle and surface wettability. Color stabilizers are sometimesadded when the anti-microbial is a silver salt.

The release rate of pharmacological additives within the lubriciouscoating and the lubricity of the coating can be controlled by theadjustment of the concentration of the urethane pre-polymer and PVP.

The lubricant coating vehicle of the present invention is generallyprepared by first obtaining a mixing vat in which to prepare thesolution. The mixing vat should be dry and free of water and alcohol.The present lubricant coating vehicle composition is preferably blendedat room temperature according to the following component ratiosdescribed as follows in weight percent: about 1 to 4 weight percent; butpreferably 1.9 weight percent polyvinylpyrrolidone, about 0.5 to 3weight percent, but preferably 1.1 weight percent of thepolyoxyethylene-based isocyanate-terminated prepolymer, about 15 to 25weight percent, but preferably 18 weight percent alkylester of acarboxylic acid and about 60 to 80 weight percent, but preferably 79weight percent toluene. The solution is mixed thoroughly until thepolyvinylpyrrolidone and the prepolymer are completely dissolved. Thecomponent blending requires approximately one hour. In some illustrativeembodiments, when the solvent system is comprised of THF its weightpercent is substantially the same as the alkylbenzene it replaces.

The resulting lubricant coating solution should appear clear to paleyellow. The coating solution is naturally moisture sensitive and willincrease in viscosity if not tightly capped during storage. Prior tocoating medical devices with the present lubricant coating solution, theparticular medical device, such as a catheter, should for best resultsbe cleaned by first filling a container with 100% isopropanol. Themedical device is then dip washed in the isopropanol for approximately 5seconds and dried by forced air at approximately 50 to 90° C. to removesurface residual isopropanol and debris. The device should at this pointbe completely isopropanol free. The medical device is then dip coatedfor about 5 to 15 seconds in the lubricant coating vehicle solution, andslowly removed from the solution vat at a rate of about 0.5 inches persecond.

The catheter or other medical device is then air dried at roomtemperature for about 10 to 30 seconds to allow any excess lubricantcoating solution to drain off. Optionally, excess lubricant may also beremoved using absorbent towels. After air drying, the coated medicaldevices are optionally but preferably baked in forced air ovens atapproximately 50° to 60° +/−5° for approximately 30 minutes to 3 hours,but most preferably for one hour, and then removed from the oven.

Curing temperature and time are dependent upon the urethane pre-polymer,solvent selection and will vary according to concentrations. Duringcuring, the diisocyanante reacts and becomes part of the polymerstructure of the medical device. The medical devices are preferablychecked for adequate transparency and to ensure that no solvent odor ispresent.

In packaging the subject medical devices coated in accordance with thepresent invention, the devices should not be allowed to touch oneanother. This is especially true if the environment humidity is high,which could cause undesirable moisture absorption by the lubricantcoating. To prevent or avoid such contact between the coated medicaldevices, each device may be packed in either paper, polyethylene tubingor the like depending on the shape of the particular device. Ifnecessary, due to high atmospheric humidity, a desiccant may likewise benecessary in the packaging.

The preferred method of making and using the lubricant coating vehicleof the present invention is described in even greater detail in thefollowing examples which are provided for purposes of furtherillustration. The following illustrative examples as described are notintended to be construed as limiting the scope of the present invention.

EXAMPLE 1

A lubricious coating was prepared by blending at room temperature thefollowing components in a mixing vat for approximately 30 minutes untilfully dissolved to form a crystal clear solution. Ingredient % (wt)Polyvinylpyrrolidone 2.0 Ethyl lactate 18.0 Toluene 77.8Isocyanate-terminated prepolymer 1.2

EXAMPLE 2

Thoracic catheters made of polyvinyl chloride (PVC) were washed withisopropanol and dried at 80° C. for 30 minutes. The catheters weredipped coated for 10 seconds while the catheters were still warm. Afterdipping, excessive coating was removed using paper towels. The catheterswere then immediately baked at 80° C. for 60 minutes. The resultantcoating was transparent and colorless with good bonding. The coating wasvery lubricious when wet and the friction reduction was up to 60%.

EXAMPLE 3

A lubricious coating vehicle was prepared by blending at roomtemperature the following components in a mixing vat for approximately60 minutes until fully dissolved to form a crystal clear to pale yellowsolution. In this illustrative example toluene was replaced with THF toachieve greater solubility of the isocyanate-terminated prepolymer. Theingredients are mixed in order given due to miscibility of antibioticsin a particular solvent. Ingredient % (wt) THF 34.0 g Pellethane@ AE80 3.0 g THF 38.0 g Tolnaftate  1.0 g NMP 20.0 g Norfloxacin  1.0 g PVPK-90  2.0 g TDI/MDI  1.0 g

The lubricious coating vehicle is prepared at room temperature.THFIPellethane @ AE80 are mixed until dissolved and mixed THF/Tolnaftatesolution is added to the Pellethane @ solution. NMPIPVP/Norfloxacin mustbe completely dissolved and then added to the above solution. Thecoating is allowed to mix for 15 minutes at room temperature and tightlycapped to prevent solvent evaporation. By adjusting the Pellethane @levels, not to exceed 5.0% and not going below 0.5%, one can adjust therelease rate of antibiotics. These antibiotics are covalently bound tothe urethane. Adjusting the PVP level does not increase or decrease therelease rate. The adjustment of the PVP level will make the device moreor less lubricious.

EXAMPLE 4

A lubricious coating vehicle, containing silver salts for use on, PVCmedical devices, is prepared by blending at room temperature thefollowing components in a mixing vat for approximately 60 minutes untilfully dissolved to form a crystal clear to pale yellow solution. Theorder combination of the ingredients is not imperative due to the lackof covalent bonding of the silver salt to the urethane. The release ofthe silver salt is regulated by Pellethane @ to PVP ratio adjustment dueto entrapment/ionic bonding of the salt. The successful silver saltsare: Giltech Powders 01-07 (this is a water soluble glass silver saltproduced by Giltech Ltd.); AlphaSan RC2000 (this is a zirconium/phosphate crystal produced by Milliken Chemical); SSD (silversulfadiazine from Kendall's Oriskany Falls, N.Y. manufacturingfacility); and silver oxide (obtained from Fisher Scientific). Heparinwas added in small quantities, 0.5-1.5%, qs.

Cyclohexanone. Ingredient % (wt) THF 46.0 g Pellethane AE80  3.0 g EthylLactate 19.0 g PVP  1.5 g Silver Salt 1.0%-3.0% Heparin 0.5%-1.5%Cyclohexanone 29.5 g MDI/TDI  1.0 g

The ingredients are mixed at room temperature in the above order. Onceboth parts have completely dissolved, the Ethyl LactateIPVP/Cyclohexanone solution was added to the THF/Pellethane mixture. Itwas found that the PVP level should not exceed approximately 2.5% as itdetrimentally affected coating adherence and silver release.Cyclohexanone was used to qs. solvent level. It is a less aggressivesolvent for Pellethane and miscible with PVP and Heparin. Depending uponthe silver complex used, the Cyclohexanone level was adjusted tomaximize coating adherence to the PVC device. The amount of silvercomplex added to the formula is determined by the overall percent ofsilver loading within the salt complex. Giltech Powders range from6%-9.5% silver loading. The particle size of silver complex is veryimportant in that it may cause problems in coating adherence. That is,larger particle size yielded poor coating adherence and uniformity. SSDhas 30% silver loading with sulfadiazine making up the bulk. AlphaSanhas a range of 6.2%-10.0% silver loading.

Bio-Compatibility Test

The coated catheters were first tested for hemolysis and then tested forlubricity using 1.) protein adsorption, and 2.) platelet adhesion. Theresults of these tests show no hemolysis and improved lubricity as notedby a reduction of protein adsorption and platelet adhesion by more than90% as set forth below.

Hemolysis

Using protein electrophoresis, no hemoglobin was seen in the supernatantof the PVPcoated thoracic catheter, nor was any seen in thehemolysis-negative control sample. As a comparison, rabbit hemoglobinwas seen in gels stained with rabbit hemoglobin and thehemolysis-positive control. The results imply that the hydrophiliccoating showed no sign of causing hemolysis.

Lubricity

Protein (fibrinogen) adsorption

Table 1 summarizes protein adsorption on the subject coated cathetersurfaces and that of the fifteen (15) control samples. TABLE 1 (1D = O.4cm, total surface area of 3.8 cm tubing = 4.7 cm2) Material n ngng/cm^(2″) Control 4 1620 ± 69  339.3 ± 14.4 PVP-coated 4 87.6 ± 27.118.3 ± 5.7

Test results show the adsorption of fibrinogen onto the hydrophilicsurface was decreased by more than 90% compared to control surface.

Platelet adhesion

Table 2 summarizes platelet adhesion on the subject coated cathetersurfaces and that of the control samples: TABLE 2 Material nPlatelet/cm²(×10⁵) Control 4 7.246 ± 0.052 PVP-coated 4 0.055 ± 0.019

Table 2 illustrates the platelet adhesion on both the PVP coated andcontrol catheters. The hydrophilic coating reduced platelet adhesion bymore than 95%. The difference in platelet adhesion was furthercharacterized by Scanning Electron Microscope (SEM) which showed controlcatheters having numerous platelets attached to the surface thereofwhile the subject PVP-coated catheters showed little sign of plateletadhesion. The subject lubricant composition prepared in accordance withthe present invention may be applied as a thin surface film, e.g., lessthan about 4.0 mil, but most preferably less than about 2.5 mil-inthickness, which upon contact with water or fluid sufficiently reducesthe coefficient of friction to aid in the in vivo placement of medicaldevices.

The unexpected significant advantages of the present lubricious coatingvehicle achieved through the particular composition formulation notedabove include decreased wet coefficient of friction, decreased adherencewith various surfaces, resistance to wet abrasion and efficaciousanti-microbial properties.

Medical devices once coated with the lubricious coating vehicle of thepresent invention are packaged and sterilized using an appropriatesterilization technique or may be sterilized and then packaged usingaseptic technique. Appropriate methods of sterilization and packagingare known to those skilled in the art and include gamma radiation,electronic beam, ethylene oxide, and like methods. Preferably, medicaldevices coated with the subject lubricious coating are packaged and thensterilized using gamma radiation by cobalt 60 with 1 to 3 mrads, butpreferably 2 mrads, in two independent exposure cycles for superiorresults.

Appropriate packaging for the subject coated medical devices includesmetallic foil pouches such as aluminum foil pouches, polyethylene film,ethylene vinyl acetate film, polypropylene film, polyvinyl chloridefilm, Tyvek@ and like packages known to those skilled in the art, butpreferably, an aluminum foil cover pouch with an ethylene vinyl acetatefilm inner liner to prevent moisture absorption by the lubricant. It iscontemplated within the scope of the present invention that somepharmaceutical additives may be light sensitive and therefore medicaldevices coated with such additives should be packaged in appropriatelight packaging known in the art.

The method of using the subject coated medical devices comprisesremoving the device from its packaging, applying moisture to thelubricated surface of the device and placing the device as necessary fora particular medical procedure.

It is seen therefore that the present lubricious coating vehicle formedical devices provides an effective wet abrasion resistant, lowcoefficient of friction coating for medical devices and a vehicle fordelivering additives such as anti-microbials and other pharmacologicalactive compounds. Additionally, the ability of the urethane within thelubricious coating vehicle to covalently bond anti-thrombogenic agentssuch as heparin is utilized to prevent systemic absorption. Thelubricious coating vehicle, the method of making and using thelubricious coating vehicle, the coated medical devices and the method ofusing the coated medical devices as disclosed and described herein havespecific advantages over the heretofore known lubricants for medicaldevices. The subject lubricious coating vehicle resists wet abrasion,adheres to a variety of surfaces, has a decreased coefficient offriction only when wetted, is biocompatible, and is able to deliverpharmacological active agents with acceptable pharmacokineticproperties. Hence for these reasons, as well as others, it is seen thatthe present lubricious coating vehicle represents a significantadvancement in the art which has substantial commercial significance.

Although the lubricious coating vehicle described in the illustrativeembodiments herein are a series of coatings pertaining to anti-microbialadditives and the methods for ensuring that the pharmacokinetics arewithin efficacious ranges, it should be appreciated that additiveswithin the lubricious coating vehicle could be other desirablepharmaceutical active compounds such as topical anesthetics,anti-inflammatory compounds both non-steroidal and steroidal,spermicidal compounds, or the like. Similarly, rather than thetraditional pharmaceutical compounds the additives can be organiccompounds with desired pharmacological effects.

It will be understood that various modifications may be made to theembodiments disclosed herein. Therefore, the above description shouldnot be construed as limiting, but merely as exemplification of thevarious embodiments. Those skilled in the art will envision othermodifications within the scope and spirit of the claims appended hereto.

1. A lubricant composition comprising: a solvent selected from the groupconsisting of tetrahydroftiran, dimethylformamide, methylene chloride,cyclohexanone, and mixtures thereof, a hydrophilic polymer other than anisocyanate-terminated prepolymer, an isocyanate-terminated prepolymerand an alkylester of a carboxylic acid selected from the groupconsisting of ethyl lactate and methylbenzoate.
 2. The composition ofclaim 1 wherein said hydrophilic polymer is selected from the groupconsisting of polyvinylpyrrolidone, polyvinyl alcohol, polyacrylic acidand polyethylene oxide.
 3. The composition of claim 1 wherein saidhydrophilic polymer is polyvinylpyrrolidone.
 4. The composition of claim1 wherein said isocyanate-terminated prepolymer is selected from thegroup consisting of polyoxyethylene-based isocyanate prepolymers,toluene and isophorone diisocyanate-based prepolymers and hexamethyleneisocyanate-terminated polyether prepolymer.
 5. The composition of claim1 wherein said solvent is a mixture comprising tetrahydrofuran andcyclohexanone.
 6. The composition of claim 1 wherein the alkylester ofcarboxylic acid is ethyl lactate.
 7. The composition of claim 1 whereinsaid solvent is a mixture comprising tetrahydroftiran and cyclohexanone,and said alkylester of carboxylic acid is ethyl lactate.
 8. Thecomposition of claim 7 wherein the hydrophilic polymer ispolyvinylpyrrolidone.
 9. A method for producing a lubricant compositioncomprising: blending a solvent selected from the group consisting oftetrahydrofuran, dimethylformamide, methylene chloride, cyclohexanone,and mixtures thereof, a hydrophilic polymer other than anisocyanate—terminated prepolymer, an isocyanate-terminated prepolymer,and an alkylester of a carboxylic acid selected from the groupconsisting of ethyl lactate and methylbenzoate.
 10. The method of claim9 wherein said hydrophilic polymer is selected from the group consistingof polyvinylpyrrolidone, polyvinyl alcohol, polyacrylic acid andpolyethylene oxide.
 11. The method of claim 10 wherein said hydrophilicpolymer is polyvinylpyrrolidone.
 12. The method of claim 9 wherein saidisocyanate-terminated prepolymer is selected from the group consistingof polyoxyethylene-based isocyanate prepolymers, toluene and isophoronediisocyanate-based prepolymers and hexamethylene isocyanate-terminatedpolyether prepolymer.
 13. The method of claim 9 wherein said solvent isa mixture comprising tetrahydrofuran and cyclohexanone.
 14. The methodof claim 9 wherein the alkylester of carboxylic acid is ethyl lactate.15. The method of claim 9 wherein said solvent is a mixture comprisingtetrahydrofuran and cyclohexanone, and said alkylester of carboxylicacid is ethyl lactate.
 16. The method of claim 15 wherein thehydrophilic polymer is polyvinylpyrrolidone.
 17. A medical device atleast partially coated with a lubricious composition comprising: asolvent selected from the group consisting of tetrahydrofuran,dimethylformamide, methylene chloride, cyclohexanone and mixturesthereof, a hydrophilic polymer other than an isocyanate-terminatedprepolymer, an isocyanate-terminated prepolymer and an alkylester of acarboxylic acid selected from the group consisting of ethyl lactate andmethyl benzoate.
 18. The medical device of claim 17 wherein thelubricious composition is further cured.
 19. The medical device of claim17, wherein said medical device is selected from the group consisting ofa catheter, an arterial venous shunt, a gastroenteric feed tube and anendotracheal tube.
 20. The medical device of claim 17, wherein saidmedical device is an urological catheter formed of polyvinyl chloride.21. The medical device of claim 17, wherein said solvent is a mixture oftetrahydrofuran and cyclohexanone, the hydrophilic polymer ispolyvinylpyrrolidone, the isocyanate-terminated prepolymer isTDI—terminated polyether based (PTMEG) prepolymer which is the reactionproduct of a diisocyanate and a polyalkylene ether glycol and thealkylester of a carboxylic acid is ethyl lactate.
 22. The lubricantcomposition of claim 1 wherein the solvent is a mixture oftetrahydrofuran and cyclohexanone, the hydrophilic polymer ispolyvinylpyrrolidone, the isocyanate-terminated prepolymer is aTDI—terminated polyether based (PTMEG) prepolymer which is the reactionproduct of a diisocyanate and a polyalkylene ether glycol, and thealkylester of a carboxylic acid is ethyl lactate.
 23. The method ofclaim 9 wherein the solvent is a mixture of tetrahydrofuran andcyclohexanone, the hydrophilic polymer is polyvinylpyrrolidone, theisocyanate-terminated prepolymer is a TDI—terminated polyether based(PTMEG) prepolymer which is the reaction product of a diisocyanate and apolyalkylene ether glycol, and the alkylester of a carboxylic acid isethyl lactate.